Decreased nitric-oxide synthase activity causes impaired endothelium-dependent relaxation in the postischemic heart
Open accessAbstract
Endothelial nitric-oxide synthase (eNOS) is an important regulator of endothelial function and vascular tone in biological tissues. While endothelial dysfunction occurs following ischemia and has been attributed to altered NO. formation, the biochemical basis for this dysfunction is unknown. Therefore, studies were performed to determine the effects of myocardial ischemia and reperfusion on eNOS in isolated rat hearts subjected to periods of global ischemia or ischemia followed by reperfusion. eNOS activity was assayed by L-[14C]arginine to L-[14C]citrulline conversion and alterations in the amount and distribution of eNOS determined by Western blotting and immunohistochemistry. While activity was preserved after 30 min of ischemia with a value of 1.1 +/- 0.1 pmol x min-1 x mg of protein-1, it decreased by 77% after 60 min and became nearly undetectable after 120 min. Reperfusion resulted in only a partial restoration of activity. The decline in activity with ischemia was due, in part, to a loss of eNOS protein. Hemodynamic studies showed that the onset of impaired vascular reactivity paralleled the loss of functional eNOS. Subjecting isolated eNOS to conditions of acidosis, which occur during ischemia, followed by restoration of pH as occurs on reperfusion, caused a combination of reversible and irreversible loss of activity similar to that seen in ischemic and reperfused hearts. Thus, loss of endothelial function following ischemia is paralleled by a loss of eNOS activity due to a combination of pH-dependent denaturation and proteolysis.
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Reports for the maximum rate of NO production by NOS vary from 1 nM/s to 70 μM/s.
“Unfortunately, the reports for the maximum rate of NO production by NOS vary from 1 nM/s to 70 μM/s [39–41].”
From Mechanisms of nitrite bioactivation (2014) · cites this paper as [40]
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References 32 · Cited by 180
Research works printed but not linked: 6
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- Authors
- Giraldez, R. R., Panda, A., Xia, Y., Sanders, S. P., & Zweier, J. L.
- Affiliations
- Johns Hopkins University (US)
- Corresponding author
- Zweier, Jay L.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1997-08
- Volume
- 272
- Issue
- 34
- Pages
- 21420-21426
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1974235853
- Cited by
- 180
- References
- 32
- Citations by year
- 2024: 1 · 2023: 4 · 2022: 2 · 2021: 6 · 2019: 5 · 2018: 10 · 2017: 6 · 2016: 5 · 2015: 7 · 2014: 10 · 2013: 6 · 2012: 6
- FWCI
- 5.09
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (HL38324)
- National Heart, Lung, and Blood Institute (HL-38324, HL52315, P50HL052315)
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Pathology and Forensic Medicine › Cardiac Ischemia and Reperfusion
- Health Sciences › Medicine › Surgery › Transplantation: Methods and Outcomes
- Keywords
- endothelial nitric oxide synthase, myocardial ischemia, ischemia-reperfusion injury, endothelial dysfunction, endothelium-dependent relaxation, nitric oxide, acidosis, protein denaturation, proteolysis, isolated rat heart, vascular reactivity
- MeSH terms
- Animals, Endothelium, Vascular, Enzyme Inhibitors, Female, Histamine, Hydrogen-Ion Concentration, Time Factors, Vasodilation, Vasodilator Agents, Blotting, Western, Reperfusion Injury, Myocardial Ischemia, Rats, Sprague-Dawley, Nitric Oxide Synthase, NG-Nitroarginine Methyl Ester, Rats
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